Case ReportGlobus Pallidus Internus Deep Brain Stimulation for DisablingDiabetic Hemiballism/Hemichorea

Byung-chul Son,1,2 Jin-gyu Choi,1 and Hak-cheol Ko1

1Department of Neurosurgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea,Seoul, Republic of Korea2Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

Correspondence should be addressed to Byung-chul Son; sbc@catholic.ac.kr

Received 22 April 2017; Revised 3 July 2017; Accepted 19 September 2017; Published 23 October 2017

Academic Editor: Mathias Toft

Copyright © 2017 Byung-chul Son et al.This is an open access article distributed under theCreative CommonsAttribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Unilateral hemichorea/hemiballism (HH) associated with contralateral neuroimaging abnormalities of the basal ganglia, which ischaracterized by T1 hyperintensity on magnetic resonance imaging (MRI) and is secondary to diabetic nonketotic hyperglycemia,is a rare and unique complication of poorly controlled diabetes mellitus (DM). Although almost all prior reports have documentedrapid resolution of HH within days after normalization of blood glucose levels, medically refractory persistent HH has been noted.The experience of surgical intervention for persistent HH is limited. A 46-year-old, right-handed female patient with type 2 DMpresented with refractory diabetic HH on the left side of 6 months’ duration despite DM control and neuroleptic medicationusage. Image-guided deep brain stimulation (DBS) on the right globus pallidus internus (GPi) was performed. A mechanicalmicropallidotomy effect was observed and chronic stimulation of GPi was quite effective in symptomatic control of diabetic HHuntil a 16-month follow-up visit. DBS of the GPi can be an effective treatment for medically refractory diabetic HH.

1. Introduction

Hemichorea/hemiballism (HH) is a hyperkinetic movementdisorder characterized by acute or subacute onset of high-amplitude, involuntary movements affecting one side of thebody [1, 2]. Ischemic/hemorrhagic stroke within the con-tralateral subthalamic nucleus (STN) and basal ganglia andnonketotic hyperglycemia are the most common causes ofHH.DiabeticHH is a unique syndrome characterized byHH,hyperglycemia, and striatal hyperintensity on T1-weightedmagnetic resonance image (MRI) [3].

The clinical course of diabetic HH is favorable and thesymptoms tend to resolve rapidly with normalization ofhyperglycemia in patients who develop diabetic HH sec-ondary to nonketotic hyperglycemia [2, 4]. However, thereare rare patients who continue to have persistent HH yearsafter the inciting hyperglycemic crisis [5]. In rare, medi-cally refractory diabetic HH, stereotactic lesioning of theventrolateral (VL) thalamus [6] and GPi [7] and DBS ofthe thalamic ventralis oralis (VO) nucleus [8] have beenreported to show significant benefit in case reports. Although

GPi DBS was reported to be effective in a patient with HHsecondary to vascular insult to the STN and substantia nigra[9], its effectiveness in diabetic HH has not yet been reported.We report the effectiveness of chronic GPi stimulation ina patient suffering refractory diabetic HH and summarizedthe utility of stereotactic surgery in this rare hyperkineticmovement disorder of metabolic cause.

2. Case Presentation

A 46-year-old, right-handed female patient with an 11-yearhistory of type 2 diabetes mellitus (DM) presented with acontinuous, violent choreic/ballistic movement of the leftarm, leg, and trunk of 6 months’ duration. At the beginning,she experienced vague discomfort in her left arm after a briefepisode of heavy lifting. An involuntary choreic movementgradually developed in her arm within several hours. Owingto cramping pain associated with a flinging movement in herleft arm and hand, she was initially treated with nonsteroidalanti-inflammatory drugs and physical therapy. However, thechoreic movement progressively worsened over the following

HindawiCase Reports in Neurological MedicineVolume 2017, Article ID 2165905, 5 pageshttps://doi.org/10.1155/2017/2165905

2 Case Reports in Neurological Medicine

(a) A T1-weighted MRI image showinghyperintensity involving the right putamenand globus pallidus. The caudate nucleus wasspared in this case

(b) An irregular area of hypointense lesionwithin the isointense putamen and globuspallidus was found on a T2-weighted MRIimage

(c) A T1-weighted MR image taken 16months after the onset of diabetic HH. T1hyperintensity in the right putamenwas stillidentified but much attenuated, comparedto the initial MRI. Note the hypointensemetallic artefact of the DBS lead (arrow)

Figure 1: Magnetic resonance imaging (MRI) findings of diabetic hemichorea/hemiballism.

2 weeks and eventually became ballistic and involved herleft arm and leg and had a high amplitude. She was admit-ted to another hospital via the emergency department forevaluation. Neurologic examination showed facial dyskinesis(grimacing) and a ballistic movement in her left trunk, arm,and legs.Themovements could not be suppressed voluntarilybut ceased during sleep. Muscle tone and strength in theupper and lower extremities were normal bilaterally. Therewas no sensory impairment and her cranial nerves werenormal. Laboratory studies revealed a fasting blood glucoselevel of 536mg/dl, a serum osmolarity of 335mOsm/kg, andanHbA1c count of 15.7%. Urinalysis was negative for ketones.There was no history of dopamine agonist or estrogenmedication use or rheumatic fever/Sydenham’s chorea.

A T1-weighted MRI image revealed a region of increasedsignal intensity restricted to the right putamen and globuspallidus, which was isointense on T2-weighted images (Fig-ure 1). No abnormal enhancement with gadolinium wasfound. Under a diagnosis of nonketotic hyperglycemic hyper-osmolar syndrome, the patient’s blood glucose level wascontrolled with subcutaneous injection of insulin.The severeballistic movement progressively improved with titrationof haloperidol (up to 10mg/day), clonazepam (6mg/day),amantadine (300mg/day), and tiapride (200mg/day) forHH. Clinical manifestations progressively improved over thecourse of 3 months of DM control with neuroleptics butdid not disappear. She suffered continuous HH, which wasmost severe in the left leg and foot and involved a severegait impairment. Finally the patient was referred to our clinicfor surgical treatment for chronic, disabling HH at 6 monthsafter the onset of diabeticHH.Considering the chronicity andmedical intractability of the situation, GPi DBS was decidedupon.

The patient underwent a stereotactic MRI scan (1.5 teslaArchieva�, Philips, Best, The Netherlands), and volumetricT1-weighted three-dimensional images, T2-weighted images,

and proton density images were obtained. The images weretransferred to a Framelink� planning station (version 4.1,Medtronic, Minneapolis, MN, USA) so that we could deter-mine the coordinates of the image-guided GPi target andwere reformatted for extraventricular trajectory planning(Figure 2(a)) [10, 11]. Implantation of the electrode (model6149, St. Jude Medical, Plano, Texas, USA) was performedunder C-arm fluoroscopy guidance under the general anes-thesia. After implantation of the lead, “O-arm” intraoperativeCT scan (Medtronic,Minneapolis,MN,USA)was performedand the images were again transferred to the Framelink�planning station and merged with the preoperative volumet-ric T1-weighted MR images to verify the location of the elec-trodes (Figure 2(b)). After verification of electrode location,the distal end of the electrode was tunneled subcutaneouslyfor external stimulation. After the patient recovered fromanesthesia, an immediate postoperative computed tomogra-phy (CT, 1mm thick axial slices) scan was taken again forverification of the location of the leadwith the preoperative T1MR images and intraoperative O-arm images (Figure 2(c)).

A prominent mechanical effect with significant reduction(50% reduction in intensity) of the choreic and proximalballistic movements was observed. Bipolar electrical stimu-lation (100–130Hz, 1–3mA, 130 usec, up to 3.5mA) furthersuppressed HH, and the hyperkinetic movements becamegrossly undetectable after 7 days of external stimulation. Nostimulation-related side effects such as dysarthria, dysphasia,or motor contraction were observed. A pulse generator(Libra�, St. Jude Medical, Plano, TX, USA) was implantedvia a transaxillary subpectoral route after 7 days of externalstimulation [12]. The patient returned to her usual activitiesand became reemployed in her previous job on diabeticmedication control and clonazepam (1.5mg/day). However,she felt continuous cramping pain and an internal sensationof muscular contraction in her lower leg and foot with-out any grossly visible choreic movements when walking.

Case Reports in Neurological Medicine 3

(a) An image in the planning software showing targetlocalization and trajectory planning for right GPiDBS. The target was directed to the posterolateralportion of the GPi which was easily identified owingto hyperintensity in the volumetric T1-weighted MRIimages

(b) An image captured from the planning software after fusion of anintraoperative O-arm CT scan with preoperative volumetric T1 images toverify the location of the implanted lead, which was taken with the patientunder general anesthesia. Although the electrode was found to be about 1mmposterior and medial to the initial target point, it was accepted

(c) An image captured from the planning software after fusion of thepostoperative CT scan with preoperative volumetric T1 images. This imagecorresponds to the center of the 2nd contact (number 2), which was used asan anode for chronic stimulation

Figure 2: Image-guided deep brain stimulation (DBS) of the globus pallidus internus (GPi) for refractory diabetic HH.

Chronic GPi stimulation was performed with regular adjust-ment of the stimulation parameters (2.6–3.0mA, 110–130Hz,110–120 usec, 1 (−), 2 (+)) every 3 months. At a 16-monthpostoperative follow-up, the patient was grossly free of HH.However, minimal chorea in the left calf and foot was noted.She was readmitted for an on and off stimulation study and afollow-upMRI examination. After 30-minute off stimulation,the ballistic movements of the left thigh, distal leg, andshoulder returned and gait difficulty was noticed along withchorea in the left foot. After 10 minutes of on stimulation, theHH in her left leg and foot disappeared almost completely.Her fasting blood glucose, serumosmolarity, andHbA1c levelwere 109mg/dl, 291mOsm/kg, and 7.9%, respectively. T1-weighted MRI images again revealed a high signal intensity

confined to the right putamen, which was greatly attenuatedcompared with that seen on the initial preoperativeMRI scan(Figures 1(a) and 1(c)).

3. Discussion

3.1. Diabetic HH. Transient chorea/ballism provoked by anepisode of nonketotic hyperglycemia has repeatedly beenreported over the past couple of decades and is the secondmost common cause of hemiballism [12]. The blood glucoselevel in patients with the condition ranges from 500 to1000mg/dL during the hyperglycemic precipitating crisis.HH is commonly associated with type 2 DM and is rarelyassociated with type 1 DM. Although diabetic HH mostly

4 Case Reports in Neurological Medicine

Table 1: Summary of stereotactic surgery for diabetic hemichorea/hemiballism.

Study/year Number ofpatients Age/sex Timing of

surgerySurgery

(lesion/DBS) Results follow-upperiod Remarks

Takamatsu et al. [6], 1995 1 57/f 1.5mo. VL lesion Excellent 4 years

Nakano et al. [8], 2005 1 65/m 5mo. VO (Voa, Vop)DBS Effective 9mo. Persistent HH in off stimulation

Goto et al. [7], 2010 1 78/f N/A GPi lesion Excellent 12mo. HH immediately disappearedCurrent case, 2017 1 46/f 6mo. GPi DBS Effective 16mo. Persistent HH in off stimulationGPi: globus pallidus internus; HH: hemichorea/hemiballism; mo: months; VL: ventral lateral nucleus; VO: ventralis oralis; Voa: ventralis oralis anterior; Vop:ventralis oralis posterior.

occurs when patients are in a state of nonketotic hyper-glycemia, some patients also have ketotic hyperglycemia [13].Themovements are typically unilateral but can be generalizedin rare cases [5]. Description of the movements ranges frommild chorea to severe ballism. According to a review of 53cases of diabetic HH [4], the average age of onset is 71, andthere is a female predominance of 1.8 : 1. Genetic factors mayplay a role, with anAsian predominance in reported cases [4].

High intensity in the basal ganglia on T1-weightedMRI isa characteristic finding in diabetic HH [2–6, 14, 15]. T1 striatalhyperintensity involves the putamen in all cases, the head ofthe caudate nucleus in most cases, and the globus pallidus ina minority of cases [14, 15]. In contrast to typical T1 hyperin-tensity, the findings on T2-weighted images are variable andrange from hyper- and iso- to hypointensity. Gradient-echoand gadolinium-enhanced T1-weighted images are reportedto be normal. Several mechanisms have been proposed toexplain T1 striatal hyperintensity, including acute ischemia,petechial microhemorrhage, injury secondary to hypervis-cosity, and vasogenic edema [14]. Currently, hyperviscosity issuggested to be the most plausible mechanism because of thefollowing findings [14]: elevated serum osmolarity at the timeof HH, variable T2-weighted MR signal changes that reflectthe difference in patterns and severity of hyperviscosity,and elevated myoinositol and choline levels seen on MRspectroscopy that are in line with a finding of abundantgemistocytes with increased protein content [14–17].

The putamen has been suggested to play a central role indiabetic HH [14]. The putamen has abundant medium-sizedspiny neurons which store and release gamma amino butyricacid (GABA) [18], and there is universal involvement ofthe putamen in diabetic HH [14, 15]. Therefore, dysfunctionof GABAergic neurons in the putamen may result in adisturbance of output nuclei of the basal ganglia, such as thesubstantia nigra and GPi [14]; resultant disinhibition of themotor thalamus ensues, leading to hyperkinetic movementdisorder.

3.2. Treatment of Diabetic HH. Diabetic HH generally re-solves over time, and often no treatment is necessary. Deter-mining the etiology of the condition is a matter of paramountimportance and correcting nonketotic hyperglycemia alongwith long-term diabetic control is the mainstay of treatment[2, 4, 12]. In cases of prolonged diabetic HH, dopaminereceptor blocking agents (chlorpromazine or haloperidol),

neuroleptics (olanzapine, clozapine), and dopamine deplet-ing agents (tetrabenazine) have been reported to be beneficial[2]. However, there are some rare patients who continue tohave persistent HH years after the inciting hyperglycemiccrisis [5].The exact incidence ofmedically refractory diabeticHH is unclear. In rare, medically refractory diabetic HH,stereotactic surgery has sporadically been reported in singlecase reports and we summarized them in Table 1.

Owing to the limited reports on surgical interventionagainst diabetic HH, the timing and type of surgery, lesion-ing, or DBS are difficult to determine. However, despitethe limited evidence, both lesioning and stimulation in theVL or VO thalamus and GPi showed good results [6–8].Because diabetic HH is especially prevalent in Asians, all3 cases regarding surgical treatment came from Japan [6–8]. We chose the GPi as a target of surgical interventionbecause previous reports regarding GPi lesioning produceduniformly positive results against diabetic HH [7] as wellas HH secondary to vascular insults involving the STN andthe brain stem [9, 19–21]. In addition, determination of thetarget within the GPi and trajectory planning was easilydone with stereotactic MR images owing to prominent T1hyperintensity in the GP (Figure 2(a)). A case of DBS ofthe VO thalamic nucleus was reported to be effective indiabetic HH [8], and we also achieved significant long-termeffectiveness with GPi stimulation. Owing to the rarity ofdiabetic HH, the present case is the first report of GPi DBS forrefractory diabetic HH. The present case showed persistentchoreiform dyskinesia during off GPi stimulation even after16 months following the onset of diabetic HH despite long-term continuous diabetic control andmedical treatment withmuch attenuation of T1 hyperintensity in the follow-up MRI.Therefore, timely surgical intervention would be of help inalleviation of disabling motor symptoms in rare patient withpersistent diabetic HH.

4. Conclusion

We report the long-term effectiveness of GPi DBS in thetreatment of chronic, disabling diabetic HH.

Conflicts of Interest

The authors declare that they have no conflicts of interestregarding this manuscript.

Case Reports in Neurological Medicine 5

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